- An analysis of the metabolites of progesterone produced by isolated Sertoli cells at the onset of gametogenesis
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Sertoli cells isolated from 7 day old rats were maintained in culture and incubated with [14C]-progesterone for 20 h. The cells and media were extracted with ether/chloroform and the extracts chromatographed two-dimensionally on TLC and the radioactive metabolites visualized by autoradiography. Nine of the metabolites (constituting about 88% of total metabolite radioactivity) were identified by relative mobilities of the compounds and their derivatives in TLC and GC systems and by recrystallizations with authentic steroids as the following: 20α-hydroxypregn-4-en-3-one, 3α-hydroxy-5α-pregnan-20-one, 5α-pregnane-3α,20α-diol, 17β-hydroxy-5α-androstan-3-one, 5α-pregnane-3,20-dione, 17-hydroxypregn-4-ene-3,20-dione, testosterone, 5α-androstane-3α,17β-diol and androst-4-ene-3,17-dione. Over 71% of the metabolite radioactivity was due to 20α-hydroxypregn-4-en-3-one, the major metabolite. 5α-reduced pregnanes constituted about 12% and C19 steroids comprised about 2.9% of the radioactivity of the metabolites. Calculation of relative steroidogenic enzyme activities from initial reaction rates suggested the following activities in μunits/mg Sertoli cell protein: 20α-hydroxysteroid oxidoreductase (20α-HSO; 7.71), 5α-reductase (4.77), 3α-HSO (3.57), 17α-hydroxylase (0.93), 17β-HSO (0.34) and C17-C20 lyase (0.34). The relatively high rate of steroidogenic enzyme activities in the Sertoli cells of young rats may indicate that Sertoli cells are less dependent on Leydig cell steroidogenesis than has been assumed. Since nearly all the metabolites of progesterone and testosterone are now identified, it is possible to construct a picture of Sertoli cell steroidogenic activity.
- Wiebe,Tilbe,Buckingham
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- Estradiol 17β-dehydrogenase and 20α-hydroxysteroid dehydrogenase from human placental cytosol: One enzyme with two activities?
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The soluble enzyme estradiol 17β-dehydrogenase (17β-ED) from human term placental cytosol is reported to be a stereospecific oxidoreductase for estrogen substrates. A published purification scheme (heat treatment and affinity chromatography) yielded a homogeneous protein which had the reported characteristics of pure 17β-ED and also had 20α-hydroxysteroid dehydrogenase (20α-HSD) activity. Spectrophotometric assay when the buffer contained albumin, 8 mg/ml, masked the 20α-HSD activity observed in albumin-free conditions and may explain why this bifunctional activity has gone unrecognized. In human placenta, one enzyme may catalyze stereospecific oxidation/reduction of both estrogen and progesterone.
- Strickler,Tobias
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- Metabolism and Effects of Progesterone in the Human Endometrial Adenocarcinoma Cell Line HEC-1
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Human endometrial adenocarcinoma cells (HEC-1 line) were incubated with 14C-progesterone.Four major labeled metabolites, 3β-hydroxy 5α-pregnan-20-one, 5α-pregnane-3β,20α-diol, 20α-hydroxy-4-pregnen-3-one and 5α-pregnane-3,20-dione were separated by thin layer chromatography, further purified by high pressure liquid chromatography, and finally identified by addition of carriers and crystallization to constant specific activity.Among these metabolites, 5α-pregnane-3β,20α-diol seems characteristic of this cell line since its formation from labeled progesterone was not detected in normal endometrium or in 2 specimens of endometrial adenocarcinoma.The growth of HEC cells was unaffected by either progesterone or medroxyprogesterone acetate, a slowly metabolized progestin, at about 10-6 M levels but was inhibited by about 10-5 M concentrations of these compounds.
- Satyaswaroop, P. G.,Frost, A.,Gurpide, E.
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- Rearrangement of 18-iodo- and 20-iodopregnanes mediated by iodosyl derivatives
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Conversion of 20-acetoxy-18-iodopregn-4-en-3-one 1 to the 18-iodosyl derivative by MCPBA resulted in a Wagner-Meerwein-type rearrangement with regioselective migration of the C13-C17 bond to give, in high yield, an abeo-pregnane in which C-18 was incorporated into ring D. The rearranged steroid was epoxidized in situ yielding a mixture of β and α 13,14-epoxides (3 and 4) which were characterized spectroscopically and by X-ray crystallography. When (20R)-20-iodopregn-4-en-3-one 9a was used as substrate, regioselective migration of the C16-C17 bond gave the D-homoandrostane with incorporation of C-20 into ring D in up to 95% yield. The 20S epimer 9b however, gave a mixture of substitution and rearrangement products. The crystal structures of the deacetylated β-epoxide 3 (5), the methanolysis product of α-epoxide 4 (7) and 20-iodopregnanes 9a and 9b are reported.
- Nicoletti,Ghini,Baggio,Garland,Burton
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- Structure and bioassay of triterpenoids and steroids isolated from sinocalamus affinis
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Five triterpenoids with a new 25-norfern carbon skeleton (1-5), a lupane triterpenoid (6), and four 20-hydroxyprogesterone acyl esters (7-10), together with 23 known compounds, were isolated from the stem (with skin removed) of Sinocalamus af f inis. The absolute configuration of compound 1 was confirmed by single-crystal X-ray crystallographic analysis using anomalous scattering of Cu Kα radiation. Compounds 1-5 exhibited inhibitory activity against protein tyrosine phosphatase 1B.
- Xiong, Liang,Zhu, Mei,Zhu, Chenggeng,Lin, Sheng,Yang, Yongchun,Shi, Jiangong
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- ANDROGENIC MODULATION OF PROGESTERONE METABOLISM BY RAT GRANULOSA CELLS IN CULTURE
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Effects of androgens on progesterone accumulation, utilization of exogenous progesterone and accumulation of progesterone metabolites by rat granulosa cells in culture were studied.Androgen increased progesterone accumulation in cultures without exogenous progesterone and slowed the overall decline of progesterone concentration in cultures supplemented with exogenous progesterone.Both aromatizable testosterone and nonaromatizable 5α-dihydrotestosterone decreased progesterone utilization by granulosa cells by 12 to 30percent.This effect was observed irrespective of whether the cells were continuously exposed to androgens or only pre-exposed.In the same experiments, androgens decreased conversion of radiolabeled progesterone to 20α-hydroxy-4-pregnen-3-one by 11 to 50percent and to 5α-pregnane-3α,20α-diol by 26 to 49percent.Accumulation of 3α-hydroxy-5α-pregnan-20-one was not altered in 3 h incubations and was increased by up to 43percent in 24 h incubations by androgen treatment.It is suggested that androgens alter progesterone catabolism by granulosa cells by decreasing 20α-hydroxysteroid dehydrogenase activity and that this effect may contribute to overall stimulatory action of androgens on progesterone accumulation.
- Duleba, Antoni J.,Takahashi, Hideyuki,Moon, Young S.
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- Isolation of 3β,20α-hydroxysteroid oxidoreductase from sheep fetal blood
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3β,20α-Hydroxysteroid oxidoreductase has been isolated from ovine fetal blood by a 2,370-fold purification scheme of ammonium sulfate fractionation, calcium phosphate gel adsorption, affinity chromatography, and fast performance liquid chromatography. A new high performance liquid chromatography-based assay for measuring 20α-reductase activity is described. The enzyme is a monomer with a molecular weight of 35,000 and uses NADPH as a cofactor for reductase activity. It reduces progesterone to 4-pregnan-20α-ol-3-one or 5α-dihydrotestosterone to 5α-androstan-3β,17β-diol with kinetic characteristics of Km = 30.8 μM and Vmax = 0.7 nmol min-1 (nmol of enzyme)-1 or Km = 74 μM and Vmax = 1.3 nmol min-1 (nmol of enzyme)-1, respectively. 5α-Dihydrotestosterone competitively inhibits 20α-reductase activity with a Ki value of 102 μM.
- Chen,Nancarrow,Sweet
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- PROGESTERONE-CATIONIC LIPID HYBRID AS ANTICANCER AGENT AND THE PROCESS OF SYNTHESIS THEREOF
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The present invention relates to the development of the cationic progesterone compounds of formula 6 as a novel anti-tumor agent. The present invention provides a method for the preparation of novel series of progesterone derivatives of formula 6. The invention also provides information related to highly selective anti-cancer activities of these compounds in wide range of cancer cell irrespective of their progesterone receptor status. Thus, the presently disclosed cationic progesterone compounds offer a viable option as anti-cancer therapeutics.
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Paragraph 0033; 0034; 0046; 0047; 0048; 0049
(2018/02/28)
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- METHODS OF NEUROPROTECTION USING NEUROPROTECTIVE STEROIDS AND A VITAMIN D
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Described herein are compositions and methods for treating or preventing nervous system injury. In particular, the methods and compositions relate to the use of at least one neuroprotective steroid, such as progesterone, and vitamin D.
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- STEROID ANALOGUES FOR NEUROPROTECTION
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Provided are steroid analogues functionalized with polar substituents at the C3 and/or C20 positions of the steroid ring system that exhibit improved water solubility. Also provided are pharmaceutical compositions comprising the steroid analogues and methods using the novel steroid analogues for the treatment and prevention of neurodegeneration in a patient following injury to the central nervous system.
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Page/Page column 107; 108
(2009/10/21)
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- Development and screening of water-soluble analogues of progesterone and allopregnanolone in models of brain injury
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Preclinical and clinical research findings have revealed that the hormone progesterone, when acutely administered, can dramatically reduce cerebral edema, inflammation, tissue necrosis, and programmed cell death following traumatic brain injury (TBI). The poor aqueous solubility of progesterone, however, limits its potential use as a therapeutic. Several chemically novel analogues of progesterone and its natural metabolite allopregnanolone have been synthesized and screened using both in vitro and whole animal models of TBI. The new derivatives demonstrated greatly improved solubility and select compounds have shown equivalent effectiveness to progesterone in reducing cerebral edema after TBI. 2009 American Chemical Society.
- MacNevin, Christopher J.,Atif, Fahim,Sayeed, Iqbal,Stein, Donald G.,Liotta, Dennis C.
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experimental part
p. 6012 - 6023
(2010/02/28)
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- An efficient enzymatic preparation of 20-pregnane succinates: chemoenzymatic synthesis of 20β-hemisuccinyloxy-5αH-pregnan-3-one
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Lipase-catalyzed transesterification of the 20 hydroxyl group in a series of pregnanes afforded novel 20-ethyl succinates that are not possible to prepare following the traditional synthetic methods. The reaction is stereoselective. The enzyme reacts selectively with the 20β epimers therefore only the 20β-succinyloxy derivatives are obtained. These compounds are obtained in variable yield, depending on the substitution in the ring A. The enzymatic approach allowed, for the first time, the synthesis of 20β-hemisuccinyloxy-5αH-pregnan-3-one, novel compound useful as a precursor of steroid-protein conjugates.
- Monsalve, Leandro N.,Machado Rada, Mayra Y.,Ghini, Alberto A.,Baldessari, Alicia
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p. 1721 - 1730
(2008/09/19)
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- PROCESS FOR PREPARING GUGGULSTERONES AND GUGGULSTEROL
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The present invention relates to a method for selective preparing 4,17 (20)-E-pregnadiene-3,16-dione (E-guggulsterone) of the formula (III) and 4,17 (20)-Z-pregnadiene-3,16-dione (Z-guggulsterone) of the formula (IV) having an effect of lowering the elevated low density lipoprotein (LDL) and high levels of the cholesterol effectively, and elevating the low levels of the high density lipoprotein (HDL) from a easy-available steroid of the following formula (I). Also, the present invention provides a method for preparation of the compound of the above formula (II).
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Page 23; 51-52
(2010/02/09)
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- 17β-aryl(arylmethyl)oxy(thio)alkyl-androstane derivatives
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The invention relates to 17β-aryl(arylmethyl)oxy(thio)alkyl-androstane derivatives having general formula (I), wherein R1is (H,OR), (H,OSO3H) or NOR; with R being H, (C1-6)alkyl or (C1-6)acyl; each of R2and R3is independently hydrogen or (C1-6)alyl; n is 0, 1, or 2; X is O, S, S(O) or S(O)2; m is 0 or 1; each of R4, R5and R6is independently hydrogen, hydroxy, (C1-4)alkoxy, halogen, NR7R8or (C1-4)alkyl, optionally substituted by hydroxy, alkoxy, halogen or oxo; each of R7and R8is independently hydrogen or (C1-4)alkyl, and wherein the dotted lines indicate a Δ7or a Δ8double bond, or a pair of conjugated double bonds selected from Δ7,14, Δ8,14and Δ6,8(14); or a pharmaceutically acceptable salt thereof. The compounds of the invention have meiosis regulating activity and can be used for the control of fertility.
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- 17β-allyloxy(thio)alkyl-androstane derivatives for the modulation of meiosis
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The invention relates to 17β-allyloxy(thio)alkyl-androstane derivatives having general formula (I) wherein R1is (H, OR), (H, OSO3H) or NOR; with R being H, (C1-6)alkyl or (C1-6)acyl; each of R2and R3is independently hydrogen or (C1-6)alkyl; n is 0, 1 or 2; X is O, S, S(O) or S(O)2; each of R4and R5is independently hydrogen or (C1-4)alkyl; each of R6, R7and R8is independently hydrogen, phenyl, halogen or (C1-4)alkyl, optionally substituted by hydroxy, (C1-4) alkoxy or halogen; or R7and R8together with the carbon atom to which they are bound form a (C3-6)cycloalkane ring; or R6and R7together with the carbon atoms to which they are bound form a (C5-6) cycloalkene ring; and wherein the dotted lines indicate a Δ7or a Δ8double bond, or a pair of conjugated double bonds selected from Δ7,14, Δ8,14and Δ6,8(14); or a pharmaceutically acceptable salt thereof. The compounds of the invention have meiosis activating activity and can be used for the control of fertility.
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- Lithium Aluminium Hydride Reduction of Pregnenolone under Conditions of Assumed Kinetic and Equilibrium Control
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Reduction of pregnenolone (1) with lithium aluminium hydride (LAH) yields pregn-5-ene-3β,20α-diol (2a) and its 20β epimer (2b) in a ratio of 1:3.8.Reduction with LAH/AlCl3 under equilibrating conditions, using an excess of 1, gave a complex product mixture containing 2a and 2b in a ratio of 1:9, pregna-3,5-dien-20-one (3), pregna-3,5-dien-20-ols (4a and 4b), pregn-4-ene-20α-ol-3-one (6a), its 20β epimer (6b) as well as small amounts of other compounds, probably pregn-4-ene-3,20-diols.A reaction scheme is presented which accounts for the formation of the various reaction products.
- Allenmark, Stig,Boren, Hans
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p. 407 - 410
(2007/10/02)
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